The universal organ donor shortage has greatly mitigated the benefits associated with organ transplantation and has led to expanding criteria for donors and lengthening lists for transplantation. A contributing factor to this resource shortage is the graft dysfunction that is observed in a high percentage of organ transplantation.
Delayed graft function (DGF) is a well-known complication affecting the kidney, heart, lung and liver allografts in the immediate post-transplantation period. The frequency of DGF ranges from 5 to 50% in deceased-donor kidney transplants. DGF is usually the result of predominant ischemic injury to the graft before and during procurement and is further aggravated by the reperfusion injury, a multi-factorial event in which immunologic factors also playa role. Indeed, ischemia and immune injury may playa synergistic pathological role in the syndrome. DGF generally leads to a more complex post-operative course for the patient. In addition, DGF is associated with prolonged hospitalization, higher transplantation costs and adverse effects on the rehabilitation of transplant recipients. The deleterious effects of DGF in the immediate post-transplant period are well known. If the ischemia reperfusion injury in DGF leads to incomplete recovery due to inability of the allograft cells to regenerate completely, then the functioning graft will have reduced survival due to reduced cellular mass. Furthermore, allo-immune responses that are known to be accentuated during DGF can contribute either to acute rejection or to accelerated cellular atrophy, reducing graft survival. On the other hand, if DGF is completely reversible, then there should be no effect of DGF on longer term graft survival. Recent evidence suggests that patients with DGF are at a 41% increased risk of graft loss at 3 years. Recent studies have attempted to use corticosteroids to prevent DGF but these interventions have not proven to be efficacious. What is needed are new methods and compositions for the prevention, inhibition, or reduction of DGF.